CPEB4 activates hundreds of genes associated with tumor growth
It has been highlighted news in the main Spanish TV and newspaper media. A study led by two researchers from Barcelona, Pilar Navarro from IMIM and Raul Mendez from IRB, shows that pancreas tumors are 80% smaller in the absence of the cytoplasmic polyadenylation element binding protein CPEB4. The results published in Nature Medicine, describe the protein CPEB4 as a “cellular orchestra conductor” that “activates” hundreds of genes associated with tumor growth.
So far, no direct link between cancers and CPEBs had been found. Nevertheless, CPEB4 is overexpressed in the studied pancreatic ductal adenocarcinoma (PDA) and glioblastoma, as well as 15 other cancers. The researchers report that its downregulation in mouse xenograft models results in a marked reduction of tumorigenic properties, primarily proliferation and vascularization, resulting in increased survival. They also show that CPEB4 is associated with a large number of transcripts in cancer cells, and, in the case of tissue plasminogen activator (tPA) mRNA, the tumor-associated overexpression of CPEB4 results in poly(A) tail elongation and translational activation, leading to abnormal overexpression of tPA in tumors.
Image: Tumorigenicity of untransfected, shCtrl, shCPEB4_2 and shCPEB4_4 RWP-1 cells (1 × 106). Cells were injected intraperitoneally, and bioluminescent activity was measured weekly. Two representative mice from each group (n = 10) after 3 weeks of injection are shown.
“In the tissues examined, pancreas and brain, CPEB4 is not detected in healthy cells but only in tumors. Thus inhibition of this protein would provide a highly specific anti-tumor treatment with few adverse effects, “one of the main drawbacks of many cancer therapies”, says Pilar Navarro, a researcher specialized in pancreatic cancer.
The study also involved Francisco X. Real, at the Centro Nacional de Investigaciones Oncológicas (CNIO) and Eduardo Eyras, ICREA researcher, both from the Department of Experimental and Health Sciences at the Universitat Pompeu Fabra (UPF), together with Mar Iglesias and Francesc Alameda from the Pathology Service at Hospital del Mar.
Ortiz-Zapater E, Pineda D, Martínez-Bosch N, Fernández-Miranda G, Iglesias M, Alameda F, Moreno M, Eliscovich C, Eyras E, Real FX, Méndez R, & Navarro P (2011). Key contribution of CPEB4-mediated translational control to cancer progression. Nature medicine PMID: 22138752